Is KRT5 p.Phe127= (c.381C>T) pathogenic?

KRT5 p.Phe127= (c.381C>T) is classified Benign/Likely benign in KRT5 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-04-01). Rare (popmax 0.111%, nfe); Associated with epidermolysis bullosa simplex.

What condition is associated with KRT5 p.Phe127= (c.381C>T)?

KRT5 p.Phe127= (c.381C>T) is associated with epidermolysis bullosa simplex (ClinVar).

How common is KRT5 p.Phe127= (c.381C>T) in the general population?

KRT5 p.Phe127= (c.381C>T) is rare (popmax 0.111%, nfe) (gnomAD).

KRT5 p.Phe127=

c.381C>T · rs150390099 · VCV309567

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.111%, nfe)

Conditions

epidermolysis bullosa simplex

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.76
Overall
CADD	11.07	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.111% European (non-Finnish) · 1,304/1,179,948 alleles

Filtering AF 0.106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.103%

Overall 0.089% 1,437/1,613,764 alleles · rare exomes 1,336/1,461,870 · genomes 101/151,894 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.111%	905
Remaining individualsnot grpmax-eligible	0.0656%	1,524
Finnishnot grpmax-eligible	0.0563%	1,777
Admixed American	0.0367%	2,727
African / African-American	0.032%	3,121
Middle Eastern	0.0165%	6,062
South Asian	0.00879%	11,378
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,602

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: KRT5
Protein: p.Phe127=
Coding: c.381C>T
MANE Select: NM_000424
dbSNP: rs150390099
Type: single nucleotide variant
Location: chr12:52519916 (GRCh38)
Gene constraint: LOEUF 0.538 · pLI 0.90 (gnomAD)
Structure: AlphaFold pLDDT 68.86 · 2 PDB
Residue 127: the 'head' region; a UniProt-annotated variant site (in ddd1)

Full KRT5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

epidermolysis bullosa simplex — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

KRT5 p.Phe127Leu Uncertain significance ★ ⚠ same residue
KRT5 p.Ala428Thr Pathogenic/Likely pathogenic ★★ same condition
KRT5 p.Ala428Val Pathogenic/Likely pathogenic ★★ same condition
KRT5 p.Glu170Lys Pathogenic ★★ same condition
KRT5 p.Glu466Gln Pathogenic/Likely pathogenic ★★ same condition
KRT5 p.Glu477Lys Pathogenic ★★ same condition
KRT5 p.Leu196Pro Pathogenic/Likely pathogenic ★★ same condition
KRT5 p.Leu463Pro Pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/krt5-p-phe127 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown